Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability [bulk RNA-seq]

ABSTRACT: In this study, we performed network analysis on Hi-C data and identified a group of non-coding regions forming many 3D contacts (referred to as hubs). Through a high-throughput CRISPR-Cas9 library screening by targeted deletion, we discovered that some hubs without any epigenetic marks were essential for cell growth and survival. Hi-C and single cell transcriptomic analyses showed that their deletion could significantly alter chromatin organization and impact the distal genes expression. This study revealed the 3D structural importance of non-coding loci that are not associated with any functional element, providing a new mechanistic understanding of disease-associated genetic variations. Furthermore, our analyses also suggest a powerful approach to develop "one-drug-multiple-targets" therapeutics targeting disease-specific non-coding regions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE176501 | GEO | 2021/08/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability [HiC]

Project description:Most non-coding regions of the human genome do not harbour any annotated element and are even not marked with any epigenomic or protein binding signal. However, an overlooked aspect of their possible role in stabilizing 3D chromatin organization has not been extensively studied. To illuminate their structural importance, we started with the non-coding regions forming many 3D contacts (referred to as hubs) and performed a CRISPR library screening to identify dozens of hubs essential for cell viability. Hi-C and single cell transcriptomic analyses showed that their deletion could significantly alter chromatin organization and impact the distal genes expression. This study revealed the 3D structural importance of non-coding loci that are not associated with any functional element, providing a new mechanistic understanding of disease-associated genetic variations (GVs), and we focused on single nucleotide variations. Furthermore, our analyses also suggest a powerful approach to develop "one-drug-multiple-targets" therapeutics targeting disease-specific non-coding regions.

2021-08-25 | GSE176500 | GEO

Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability [single-cell RNA-seq]

2021-08-25 | GSE176502 | GEO

Sex-determining 3D regulatory hubs revealed by genome spatial auto-correlation analysis [RNA-seq]

Project description:Mammalian sex is determined by a network of antagonistic genes that are well characterized. However, its non-coding regulation is still largely unknown. Here we explore the 3D chromatin landscape of sex determination in vivo. We integrate Hi-C with ChIP-seq experiments using METALoci, a novel genome spatial auto-correlation analysis approach that identifies 3D regulatory hubs across the genome. We uncover a prominent rewiring of chromatin interactions during sex determination. By combining predictive approaches and validations in transgenic mice we identify a novel Fgf9 regulatory hub, which deletion results in male-to-female sex reversal.

2022-11-21 | GSE217617 | GEO

Sex-determining 3D regulatory hubs revealed by genome spatial auto-correlation analysis [Hi-C]

2022-11-21 | GSE217616 | GEO

Unbiased Capture Hi-C reveals the potential targets of breast cancer susceptibility loci

Project description:Genome-wide association studies have identified over 70 common variants that are associated with breast cancer risk. Most of these variants map to non-protein-coding regions; several map to gene deserts, regions of several hundred kb lacking protein-coding genes. We hypothesized that gene deserts harbour long-range regulatory elements that can physically interact with target genes to influence their expression. To test this, we developed Capture Hi-C (CHi-C), which by incorporating a sequence capture step into a Hi-C protocol, allows high-resolution analysis of targeted regions of the genome. We used CHi-C to investigate long-range interactions at three breast cancer gene deserts mapping to 2q35, 8q24.21 and 9q31.2. We identified interaction peaks between putative regulatory elements ("bait fragments") within the captured regions and "targets" that included both protein-coding genes and long non-coding (lnc)RNAs, over distances of 6.6 kb to 2.6 Mb. Target protein-coding genes were IGFBP5, KLF4, NSMCE2 and MYC; target lncRNAs included DIRC3, PVT1 and CCDC26. For two gene deserts we were able to define a set of SNPs that were correlated with the published risk variant and that clustered within the bait end of an interaction peak. Preliminary functional analyses implicate one SNP (rs12613955; 2q35) as a potentially functional variant. Capture Hi-C was carried out in BT483, SUM44, and GM06990 cell lines to investigate breast cancer risk loci 2q35, 8q24.21 and 9q31.2.

2014-08-04 | E-GEOD-55634 | biostudies-arrayexpress

Unbiased Capture Hi-C reveals the potential targets of breast cancer susceptibility loci

2014-08-04 | GSE55634 | GEO

Targeting the 3D genome by anthracyclines for chemotherapeutic effects

Project description:The chromatins are folded into three-dimensional (3D) structures inside cells, which coordinates the regulation of gene transcription by the non-coding regulatory elements. Aberrant chromatin 3D folding has been shown in many diseases, such as acute myeloid leukemia (AML), and may contribute to tumorigenesis. The anthracycline topoisomerase II inhibitors can induce histone eviction and DNA damage. We performed genome-wide high-resolution mapping of the chemotherapeutic effects of various clinically used anthracycline drugs. ATAC-seq was used to profile the histone eviction effects of different anthracyclines. TOP2A ChIP-seq was used to profile the potential DNA damage regions. Integrated analyses show that different anthracyclines have distinct target selectivity on epigenomic regions, based on their respective ATAC-seq and ChIP-seq profiles. We identified the underlying molecular mechanism that unique anthracycline variants selectively target chromatin looping anchors via disrupting CTCF binding, suggesting an additional potential therapeutic effect on the 3D genome. We further performed Hi-C experiments, and data from K562 cells treated with the selective anthracycline drugs indicate that the 3D chromatin organization is disrupted. Furthermore, AML patients receiving anthracycline drugs showed altered chromatin structures around potential looping anchors of, which linked to distinct clinical outcomes. Our data indicate that anthracyclines are potent and selective epigenomic targeting drugs and can target the 3D genome for anticancer therapy, which could be used for personalized medicine to treat tumors with aberrant 3D chromatin structures

2025-01-06 | GSE276066 | GEO

Sex-determining 3D regulatory hubs revealed by genome spatial auto-correlation analysis [Hi-C]

Project description:Sex-determining 3D regulatory hubs revealed by genome spatial auto-correlation analysis [Hi-C]

| PRJNA899840 | ENA

Whole genome shotgun bisulfite sequencing of the Lsh-/- and Lsh+/+ murine embryonic fibroblasts and ES cells

Project description:Whole-genome single-base resolution methylcytosine map reveals profound changes that occur after Lsh deletion during embryonic development in primary WT and Lsh-/- MEFs. Lsh deletion leads to widespread decreases of CG methylation level at uniquely mapped genomic regions compared to wild type, including TSSs at protein-coding genes, and non-coding RNA genes. MethylC-Seq from Mus musculus primary MEFs.

2014-06-13 | E-GEOD-57486 | biostudies-arrayexpress

Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability

Project description:Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability

| PRJNA736443 | ENA